SPINK1 immunohistochemistry: An ancillary tool to diagnose urothelial carcinoma in situ and urothelial dysplasia Journal Article


Authors: Khani, F.; Beg, S.; Park, K.; Kawaguchi, K.; Chiu, Y. L.; Robinson, B. D.; Lis, R.; Stack, E. C.; Scherr, D. S.; Rosenberg, J. E.
Article Title: SPINK1 immunohistochemistry: An ancillary tool to diagnose urothelial carcinoma in situ and urothelial dysplasia
Abstract: Expression of SPINK1 (Serine protease inhibitor Kazal type I), also known as tumor associated trypsin inhibitor (TATI), has been demonstrated in a wide spectrum of benign, inflammatory, and neoplastic conditions. Based on our prior results of its expression in urothelial carcinoma, in this study we further characterized SPINK1 expression in a spectrum of urothelial lesions and investigated its potential diagnostic utility. A total of 396 samples comprising a spectrum of urothelial lesions including benign, premalignant, and malignant lesions were evaluated for SPINK1 expression by immunohistochemistry and amplification by fluorescence in situ hybridization (FISH). In a subset of lesions, immunohistochemistry for CK20, CD44, and p53 was also performed. SPINK1 expression was restricted to umbrella cells or lost in 93 % of normal urothelium. Overexpression of SPINK1 in reactive urothelial atypia, urothelial dysplasia, carcinoma in situ (CIS), and papillary urothelial carcinoma (invasive and non-invasive) was seen in 21 %, 36 %, 87 % and 54 % of cases, respectively. Increasing frequency of SPINK1 loss was observed with higher pathologic stage (48.5 % in pT1, 50 % in pT2, 62.5 % in pT3). When compared with other markers, SPINK1 positivity itself has a sensitivity of 90 % for detecting CIS, a 97 % sensitivity when combined with CK20, and a 98 % sensitivity when combined with p53. No amplification of SPINK1 was detected by FISH in any case. Our study illustrates the differential expression of SPINK1 in various urothelial lesions and shows that SPINK1 immunohistochemistry can be utilized as an ancillary tool with high sensitivity and specificity for diagnosing urothelial dysplasia and CIS in challenging cases. This record is sourced from MEDLINE/PubMed, a database of the U.S. National Library of Medicine
Keywords: immunohistochemistry; adult; clinical article; controlled study; human tissue; aged; sensitivity and specificity; aprotinin; cohort analysis; protein p53; urothelium; fluorescence in situ hybridization; diagnostic value; carcinoma in situ; diagnosis; urothelial carcinoma; transitional cell carcinoma; dysplasia; bladder biopsy; human; male; female; article; urothelial carcinoma in situ; spink1; carcinoma in situ (cis); psti; tati; serine peptidase inhibitor kazal type
Journal Title: Pathology Research and Practice
Volume: 273
ISSN: 16180631
Publisher: Unknown  
Date Published: 2025-01-01
Start Page: 156148
Language: English
DOI: 10.1016/j.prp.2025.156148
PUBMED: 40743580
PROVIDER: scopus
PMCID: PMC12365953
DOI/URL:
Notes: Article -- Source: Scopus
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